10110229Integrating cutting-edge profiling platforms to improve the accuracy of blood-based diagnosis for Ovarian CancerClosedLaunchpadInnovate UKOvarian Cancer is notoriously difficult to diagnose, with the majority of diagnoses achieved only in the later stages of the disease. The current blood marker, CA125, is not fit for purpose as it cannot detect up to 50% of early stage Ovarian Cancers, and its levels are not elevated in up to 20% of confirmed late stage Ovarian Cancers. Whilst CA125 is considered to have limited use as a monitoring tool to assess treatment responses, or to detect recurrence following treatment, its low level of accuracy means that it cannot be considered useful as a diagnostic test. We have identified a number of promising biomarkers based on the DNA methylation (DNAme) events which occur in ovarian cancer. In tissues we observed that these DNAme events happen at very early stages, and are maintained, or often elevated further, as ovarian cancer progresses. DNAme markers can be detected with high accuracy, from very low levels of tissue DNA (lower than 1ng), using a Droplet Digital PCR (ddPCR) approach. However, we have shown that these markers are often not conserved in a blood sample, owing to the nature by which circulating tumour DNA (ctDNA) is degraded in blood, and becoming impossible to detect by ddPCR. This leads us to conclude that more detailed knowledge about how ctDNA behaves in the blood would provide a significant technical advance in enabling the optimal detection of DNAme markers, and drastically improving Ovarian Cancer diagnosis. GenoME will utilise the latest DNAme profiling technology, coupled with high resolution 'fragmentomic' sequencing of ctDNA fragments, to reveal which regions of cfDNA are protected from degradation in the bloodstream of Ovarian Cancer patients. Fine mapping of these protected regions will allow us to identify highly conserved DNAme biomarker sequences across cfDNA representative of a broad patient population. Furthermore this will allow us to combine several DNAme markers together, significantly improving the rate of clinical accuracy and diagnosis, and providing greater coverage across Ovarian Cancer. This approach has potential to offer a game changing shift in patient outcomes via the early diagnosis and treatment intervention of Ovarian Cancer.